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Intrathecal Injection of the [final sigma]1 Receptor Antagonist BD1047 Blocks Both Mechanical Allodynia and Increases in Spinal NR1 Expression during the Induction Phase of Rodent Neuropathic Pain
Cited 109 time in
Web of Science
Cited 110 time in Scopus
- Authors
- Issue Date
- 2008
- Publisher
- Lippincott, Williams & Wilkins
- Citation
- Anesthesiology 2008; 109:879-89
- Abstract
- Background: Selective blockade of spinal 1 receptors (Sig-
1R) suppresses nociceptive behaviors in the mouse formalin
test. The current study was designed to verify whether intrathecal
Sig-1R antagonists can also suppress chronic neuropathic
pain.
Methods: Neuropathic pain was produced by chronic constriction
injury (CCI) of the right sciatic nerve in rats. The Sig-1R
antagonist BD1047 was administered intrathecally twice daily
from postoperative days 0 to 5 (induction phase of neuropathic
pain) or from days 15 to 20 (maintenance phase). Western blot
and immunohistochemistry were performed to determine
changes in Sig-1R expression and to examine the effect of
BD1047 on N-methyl-D-aspartate receptor subunit 1 expression
and phosphorylation in spinal cord dorsal horn from neuropathic
rats.
Results: BD1047 administered on postoperative days 0–5 significantly
attenuated CCI-induced mechanical allodynia, but not
thermal hyperalgesia, and this suppression was blocked by
intrathecal administration of the Sig-1R agonist PRE084. In contrast,
BD1047 treatment during the maintenance phase of neuropathic
pain had no effect on mechanical allodynia. Sig-1R
expression significantly increased in the ipsilateral spinal cord
dorsal horn from days 1 to 3 after CCI. Importantly, BD1047 (30
nmol) administered intrathecally during the induction, but not
the maintenance phase, blocked the CCI-induced increase in
N-methyl-D-aspartate receptor subunit 1 expression and phosphorylation.
Conclusions: These results demonstrate that spinal Sig-1Rs
play a critical role in both the induction of mechanical allodynia
and the activation of spinal N-methyl-D-aspartate receptors
in CCI rats and suggest a potential therapeutic role for the
use of Sig-1R antagonists in the clinical management of neuropathic
pain.
- ISSN
- 0003-3022
- Language
- English
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